ABSTRACT Alzheimer's disease prevalence is expected to triple by 2050, and current medications do not change the disease course. However, recent studies have projected that up to 30% of Alzheimer's disease may be preventable by targeting modifiable risk factors. Indeed, population-based studies are finding that, although the total number of dementia cases is growing, age-specific incidence rates are declining in parallel with population-level reductions in risk factors such as low education, smoking and cardiovascular disease. Furthermore, studies in Europe have demonstrated slower cognitive decline and less cognitive impairment with multi-domain risk reduction interventions. Given the importance of Alzheimer's prevention and the potential benefits of risk reduction for general as well as brain health, even relatively small reductions in Alzheimer's incidence would have a dramatic public health impact. Despite the tremendous promise of the multi-domain risk reduction approach, no primary prevention trials have been performed in the U.S. We propose to conduct a pilot study of a multi-domain Alzheimer's disease risk reduction intervention in the U.S. To maximize feasibility and the potential for implementation, we propose to perform our trial within an integrated healthcare delivery system. In addition, we plan to utilize a personalized intervention, which has proven successful in the healthcare setting for managing conditions such as depression and hypertension, and which should yield greatest change on risk factors. Specifically, we propose to randomize 200 higher-risk older adults (age ?70 with subjective cognitive complaints, performance in the lower end of normal on a cognitive test and ? 2 modifiable risk factors that will be targeted by our intervention) to a two year Multi-domain Alzheimer's Risk Reduction Study (MARRS) intervention or a Health Education (HE) control. In the MARRS intervention group, the team will work with participants to develop a personalized action plan to address risk reduction including cardiovascular risk management; smoking cessation; physical, mental and social activity; healthy diet; improved sleep quality and medication management. The goals of our study are to collect pilot data on the effect of MARRS on 2-year rate of cognitive decline compared to HE (Aim 1); compare changes in Alzheimer's modifiable risk factors (Aim 2); and gather preliminary data on the effect of MARRS versus HE on other important health-related outcomes (Aim 3). We will also compare strategies for identifying higher-risk patients for this and future studies. This innovative pilot trial will provide critically needed information to support a future multi-site trial, with the ultimate goal of delaying or preventing cognitive decline leading to Alzheimer's disease.